Method for hydrogenating unsaturated esters

Abstract

The present invention relates to a method for hydrogenating an ester-containing substrate. More particularly, the present invention relates to a method for reducing an α,β-γ,δ unsaturation-containing ester of formula (I) and a β,γ unsaturation-containing ester to produce an alcohol of formula (II). The method of the present invention uses a base, the conjugate acid of which has a pKa of 4 to 15. The method of the present invention finds use in the synthesis of organic molecules.

Description

[Technical field]

[0001] TECHNICAL FIELD TO WHICH THEINVENTION BELONGS The present invention relates to a process for the hydrogenation of ester-containing substrates. More particularly, the present invention relates to a process for the reduction of esters containing α,β-γ,δ unsaturation and esters containing β,γ unsaturation.

[0002] 2. Background of the Invention The reduction of esters is an essential transformation in the chemical industry as a route to primary alcohols. The reduction of esters has traditionally been carried out using reagents such as sodium metal (in stoichiometric or excess amounts) in ethanol (Bouveault-Blanc reduction) or, more recently, LiAlH 4 or NaBH 4 These reduction reactions have been carried out using metal hydride reagents such as 1,2-dichlorophenyl ether, 1,2-dichlorophenyl ether, and 1,2-dichlorophenyl ether. However, these reduction reactions are difficult to carry out effectively on a large scale, especially due to safety concerns associated with the extremely exothermic quenching step. Thus, research on the reduction of esters has more recently focused on catalytic reduction using hydrogen gas. For example, Cu or Zn-based heterogeneous catalysts have been used on a very large scale for ester reduction, mainly in the natural detergent alcohol (NDA) market. However, these methods require very high pressures and / or temperatures in addition to large-scale dedicated production facilities. Also, the chemoselectivity of ester reduction compared to other sensitive functional groups can be problematic when using these methods.

[0003] The reduction of unsaturated esters, such as α,β-γ,δ and β,γ unsaturated esters, can be particularly problematic. Finding conditions that chemoselectively reduce the ester group while preserving the regiochemistry of the alkenyl functionality is particularly difficult.

[0004] As will be readily understood, α, β, γ, and δ refer to the carbon atoms in an ester-containing substrate when used in the context of an unsaturated ester. α, β, γ, and δ are used to indicate the carbon atom at which an alkene (C=C) or alkyne (C≡C) bond is present. Scheme 1 below shows the positions of the α, β, γ, and δ carbons in a typical ester-containing substrate, and this convention is used herein and throughout. Thus, for example, a β,γ-unsaturated ester contains an alkene bond between the β and γ carbons, while an α,β-γ,δ unsaturated ester contains two alkene bonds (i.e., an alkene bond between the α and β carbons, and an alkene bond between the γ and δ carbons). [ka]

[0005] Many methods for ester hydrogenation using transition metal catalysts have been developed, however, these methods often result in the reduction of the alkenyl functionality or alteration of the regiochemistry of the alkenyl functionality.

[0006] Thus, there remains a need for methods capable of selectively reducing unsaturated esters, particularly α,β-γ,δ unsaturated esters and β,γ unsaturated esters, while preserving the regiochemistry of the alkenyl functionality. Summary of the Invention

[0007] Thus, the present invention provides a method for hydrogenating α,β-γ,δ unsaturated esters or β,γ unsaturated esters, which has high chemoselectivity for hydrogenating the ester groups of α,β-γ,δ unsaturated esters and β,γ unsaturated esters to the corresponding alcohols while maintaining the regiochemistry and / or stereochemistry of the alkenyl and / or alkynyl functional groups.

[0008] In a first aspect of the present invention, there is provided a process for hydrogenating an ester-containing substrate of formula (I) to produce an alcohol of formula (II): [ka] The method comprises treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen; The ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester; R u is an organic group having 3 to 70 carbon atoms, provided that R u is the carbonyl carbon of the ester moiety ( * ) to form an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester of formula (I); R v is an organic group having 1 to 70 carbon atoms; The conjugate acids of the bases have pKa's between 4 and 15.

[0009] A surprising advantage of the present invention is that the hydrogenation of α,β-γ,δ unsaturated esters or β,γ unsaturated esters is carried out by the addition of R u The reaction proceeds without reducing the alkenyl functionality of the R u The regiochemistry and / or stereochemistry of the R groups are maintained. uThe groups are the same in the ester-containing substrate of formula (I) and the alcohol of formula (II). The conjugate acid of the base of the present invention has a pKa of 4-15 and can be considered a weak base. Without wishing to be bound by any theory, it is believed that the use of a base whose conjugate acid has a pKa of 4-15 in the hydrogenation process of the present invention prevents conjugation of the carbonyl group with the alkenyl functionality, minimizing or preventing the formation of enolate intermediates. It is speculated that the formation of such enolate intermediates may be responsible for the reduction of the alkenyl functionality and the loss of regiochemistry of the alkene. Furthermore, it is believed that the formation of enolate intermediates may cause the formation of other undesirable by-products, such as those resulting from cycloaddition reactions (e.g., Diels-Alder) or condensation reactions. It is further surprising that the activity of the transition metal catalyst is activated and maintained by the use of a base whose conjugate acid has a pKa of 4-15 in the hydrogenation process of the present invention.

[0010] Transition metal-catalyzed reduction of cinnamic acid esters containing α,β-unsaturated esters has been reported (e.g., de Vries et al., Adv. Synth. Catal. 2018, 360). However, conditions that may be suitable for hydrogenating cinnamic acid esters may not be suitable for ester-containing substrates of formula (I). In other words, we do not believe that cinnamic acid esters form enolate intermediates during the hydrogenation process carried out under basic conditions, and therefore do not suffer from the same problems as ester-containing substrates of formula (I), as described above. [Brief description of the drawings]

[0011] [Figure 1] FIG. 1 shows an exemplary reaction scheme for the conversion of an ester-containing substrate of formula (I) to the corresponding alcohol of formula (II).

[0012] definition The point of attachment of a moiety or substituent is represented by "-". For example, -OH is attached through an oxygen atom.

[0013] Unless expressly stated otherwise, structures depicted herein include all conformational or geometric isomers of said structure. For example, when an alkene double bond is shown, both the E and Z (or cis and trans) isomers are intended and included, and when more than one alkene double bond is shown, all conformational or geometric isomers of the structure are included and intended (e.g., E,E; E,Z; Z,E; and Z,Z; as well as cis, cis; cis, trans; trans, cis; and trans, trans).

[0014] As used herein, the terms "maintenance of regiochemistry" and "retention of regiochemistry" refer to the maintenance or retention of the position of any given functional group, e.g., a β,γ alkene bond.

[0015] As used herein, the term "geometry" is used to refer to the geometric or conformational structure of a molecule or functional group, for example, the conformation of an E or Z (or cis or trans) alkene bond.

[0016] As used herein, the term "alkyl" may include linear or branched saturated hydrocarbon groups. In certain embodiments, an alkyl group may have 1-20 carbon atoms, in certain embodiments, 1-15 carbon atoms, and in certain embodiments, 1-8 carbon atoms. An alkyl group may be unsubstituted. Alternatively, an alkyl group may be substituted. Unless otherwise specified, an alkyl group may be attached at any suitable carbon atom, and if substituted, may be substituted at any suitable atom. Typical alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.

[0017] As used herein, the term "alkenyl" refers to a straight-chain or branched unsaturated hydrocarbon group containing at least one carbon-carbon double bond.

[0018] As used herein, the term "alkynyl" refers to a straight-chain or branched unsaturated hydrocarbon group containing at least one carbon-carbon triple bond.

[0019] As used herein, the term "cycloalkyl" is used to denote a saturated carbocyclic hydrocarbon group. Cycloalkyl groups can have a single ring or multiple condensed rings. In certain embodiments, cycloalkyl groups can have 3 to 15 carbon atoms, in certain embodiments, 3 to 10 carbon atoms, and in certain embodiments, 3 to 8 carbon atoms. Cycloalkyl groups can be unsubstituted. Alternatively, cycloalkyl groups can be substituted. Unless otherwise specified, cycloalkyl groups can be attached at any suitable carbon atom and, if substituted, can be substituted at any suitable atom. Exemplary cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, adamantyl, and the like.

[0020] As used herein, the term "cycloalkenyl" refers to an unsaturated, non-aromatic carbocyclic ring. Thus, a cycloalkenyl group has at least one carbon-carbon double bond, but may have more. In certain embodiments, a cycloalkenyl group may have 3 to 15 carbon atoms, in certain embodiments, 3 to 10 carbon atoms, and in certain embodiments, 3 to 8 carbon atoms. A cycloalkenyl group may be unsubstituted. Alternatively, a cycloalkenyl group may be substituted. Unless otherwise specified, a cycloalkenyl group may be attached at any suitable carbon atom, and if substituted, may be substituted at any suitable atom. Exemplary cycloalkenyl groups include, but are not limited to, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.

[0021] As used herein, the term "alkoxy" refers to an optionally substituted group of formula alkyl-O or cycloalkyl-O-, where alkyl and cycloalkyl are as defined above.

[0022] As used herein, the term "aryl" refers to an aromatic carbocyclic group. An aryl group may have a single ring or multiple fused rings. In certain embodiments, an aryl group may have 6-20 carbon atoms, in certain embodiments, 6-15 carbon atoms, and in certain embodiments, 6-12 carbon atoms. An aryl group may be unsubstituted. Alternatively, an aryl group may be substituted. Unless otherwise specified, an aryl group may be attached at any suitable carbon atom, and if substituted, may be substituted at any suitable atom. Examples of aryl groups include, but are not limited to, phenyl, naphthyl, anthracenyl, and the like.

[0023] As used herein, the term "arylalkyl" refers to an optionally substituted group of formula aryl-alkyl-, where aryl and alkyl are as defined above.

[0024] As used herein, the terms "halogen", "halo" or "hal" refer to -F, -Cl, -Br and -I.

[0025] As used herein, the term "heteroalkyl" refers to a linear or branched saturated hydrocarbon group in which one or more carbon atoms are independently replaced with one or more heteroatoms (e.g., nitrogen, oxygen, phosphorus, and / or sulfur atoms). A heteroalkyl group may be unsubstituted. Alternatively, a heteroalkyl group may be substituted. Unless otherwise specified, a heteroalkyl group may be attached at any suitable atom, and if substituted, may be substituted at any suitable atom. Examples of heteroalkyl groups include, but are not limited to, ethers, thioethers, primary amines, secondary amines, tertiary amines, and the like.

[0026] As used herein, the term "heterocycloalkyl" refers to a saturated cyclic hydrocarbon group in which one or more carbon atoms are independently replaced with one or more heteroatoms (e.g., nitrogen, oxygen, phosphorus, and / or sulfur atoms). Heterocycloalkyl groups may be unsubstituted. Alternatively, heterocycloalkyl groups may be substituted. Unless otherwise specified, heterocycloalkyl groups may be attached at any suitable atom, and if substituted, may be substituted at any suitable atom. Examples of heterocycloalkyl groups include, but are not limited to, epoxide, morpholinyl, piperadinyl, piperazinyl, thiiranyl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, thiazolidinyl, thiomorpholinyl, and the like.

[0027] As used herein, the term "heteroaryl" refers to an aromatic carbocyclic group in which one or more carbon atoms are independently replaced by one or more heteroatoms (e.g., nitrogen, oxygen, phosphorus, and / or sulfur atoms). Heteroaryl groups may be unsubstituted. Alternatively, heteroaryl groups may be substituted. Unless otherwise specified, heteroaryl groups may be bonded at any suitable atom, and if substituted, may be substituted at any suitable atom. Examples of heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, thiophenyl, oxadiazolyl, pyridinyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, quinolinyl, and the like.

[0028] As used herein, the term "heterocycle" encompasses both heterocycloalkyl and heteroaryl groups.

[0029] As used herein, the term "substituted" refers to a group in which one or more hydrogen atoms are each independently replaced with the same or different substituents (e.g., 1, 2, 3, 4, 5 or more). Examples of substituents include -halo, -C(halo), 3 , -R c , =O, =S, -OR c , -SR c , -NR c R d , -CN, -NO 2 , -C(O)-R c , -COOR d , -C(S)-R c , -C(S)OR d , -S(O) 2 OH, -S(O) 2 -R c , -S(O) 2 NR c R d , -OS(O)-R c and -CONR c R d , e.g., -Halo, -C(Halo) 3 (For example, -CF 3 ), -R c , -OR c , -NR c R d , -CN, or -NO 2 These include, but are not limited to, R c and R d is independently selected from the group consisting of H, alkyl, aryl, arylalkyl, heteroalkyl, heteroaryl, or R c and R d R together with the atom to which they are attached form a heterocycloalkyl group. c and R d may be unsubstituted or further substituted as defined herein.

[0030] As used herein, the term "fatty acid" refers to a carboxylic acid having a long aliphatic chain (e.g., more than 6 carbon atoms) that can be either saturated or unsaturated. The aliphatic chain of the fatty acid can be branched or unbranched. In certain embodiments, the aliphatic chain of the fatty acid comprises 12-24 carbon atoms. In certain embodiments, the aliphatic chain of the fatty acid comprises 0-5 carbon-carbon double bonds.

[0031] As used herein, the term "fatty alcohol" refers to an alcohol having a long aliphatic chain (e.g., more than 6 carbon atoms) that can be either saturated or unsaturated. The aliphatic chain of the fatty alcohol can be branched or unbranched. In certain embodiments, the aliphatic chain of the fatty alcohol comprises 12-24 carbon atoms. In certain embodiments, the aliphatic chain of the fatty alcohol comprises 0-5 carbon-carbon double bonds.

[0032] As used herein, the term "wax ester" or "waxy ester" refers to an ester of a fatty acid and a fatty alcohol, where the fatty acid and fatty alcohol are as defined above.

[0033] As used herein, the term "bidentate ligand" refers to a ligand that donates two pairs of electrons to a metal atom.

[0034] As used herein, the term "tridentate ligand" refers to a ligand that donates three pairs of electrons to a metal atom.

[0035] As used herein, the term "tetradentate ligand" refers to a ligand that donates four pairs of electrons to a metal atom.

[0036] As used herein, the term "Ru-SNS" refers to dichlorotriphenylphosphine[bis(2-(ethylthio)ethyl)amine]ruthenium(II).

[0037] As used herein, the term "Ru-PNN" refers to dichlorotriphenylphosphine [2-(diphenylphosphino)-N-(2-pyridinylmethyl)ethanamine]ruthenium(II).

[0038] As used herein, the term "Ru-SNN" refers to dichlorotriphenylphosphine[2-(ethylthio)-N-(2-pyridinylmethyl)ethanamine]ruthenium(II).

[0039] As used herein, the term "S / C" is an abbreviation for "substrate / catalyst" and is used to represent the catalyst loading used in a reaction, i.e., the molar ratio of ester-containing substrate to catalyst present in the reaction mixture. If the ester-containing substrate contains more than one ester moiety, the S / C value is adjusted accordingly. For example, a triglyceride to catalyst molar ratio of 10,000:1 is equivalent to an S / C of 30,000:1 (because the triglyceride substrate contains three ester moieties).

[0040] As used herein, the term "turnover number" (TON) refers to the number of moles of substrate that one mole of catalyst can convert before it is deactivated.

[0041] As used herein, unless otherwise specified, "mol %" refers to the molar amount of a specified substance (e.g., base) as a percentage relative to the molar amount of the ester-containing substrate. The "mol %" amount given for a particular substance (e.g., base) is the amount of that substance used in the reaction chamber (i.e., where the hydrogenation reaction occurs).

[0042] As used herein, the term "hydrogenation" refers to hydrogenation using molecular hydrogen.

[0043] Detailed Description of the Invention Preferred and / or optional features of the invention are presented herein. Any aspect of the invention may be combined with any other aspect of the invention, unless the context requires otherwise. Any preferred and / or optional features of any aspect may be combined, either alone or in combination with any aspect of the invention, unless the context requires otherwise.

[0044] The present invention provides a process for hydrogenating an ester-containing substrate of formula (I) to produce an alcohol of formula (II): [ka] The method comprises treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen; The ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester; R u is an organic group having 3 to 70 carbon atoms, provided that R u is the carbonyl carbon of the ester moiety ( * ) to form an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester of formula (I); R v is an organic group having 1 to 70 carbon atoms; The conjugate acids of the bases have pKa's between 4 and 15.

[0045] Ester-Containing Substrates The method of the invention involves the hydrogenation of an ester-containing substrate of formula (I), the ester-containing substrate of formula (I) comprising an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester. The ester-containing substrate of formula (I) comprises at least one ester moiety.

[0046] In a preferred method of the invention, the ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester. In a preferred method of the invention, the ester-containing substrate of formula (I) comprises a β,γ unsaturated ester.

[0047] In a preferred method of the present invention, the ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester, and the bond between the α carbon atom and the β carbon atom and the bond between the γ carbon atom and the δ carbon atom in the α,β-γ,δ unsaturated ester, or the bond between the β carbon atom and the γ carbon atom in the β,γ unsaturated ester, are alkenyl bonds, respectively. When the ester-containing substrate of formula (I) is an α,β-γ,δ unsaturated ester, it may be preferred that the α,β-γ,δ unsaturated ester has a cis, cis configuration, a cis, trans configuration, a trans, cis configuration, or a trans, trans configuration. When the ester-containing substrate of formula (I) is a β,γ unsaturated ester, it may be preferred that the β,γ unsaturated ester has a cis configuration or a trans configuration.

[0048] The ester-containing substrate has the formula (I): [ka] (In the formula, R u is an organic group having 3 to 70 carbon atoms, provided that R u is the carbonyl carbon of the ester moiety ( * ) to form an α,β-δ,γ unsaturated ester or a β,δ unsaturated ester of formula (I); R v is an organic group having 1 to 70 carbon atoms.

[0049] As will be understood, R u is the carbonyl carbon ( * ) to form an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester.

[0050] In a preferred method of the present invention, R u sp 2 Terminal CH with hybridized carbon atoms 2 Thus, in a preferred method of the present invention, R u However, the carbonyl carbon of the ester moiety ( *) to form an α,β-δ,γ unsaturated ester or a β,δ unsaturated ester of formula (I), R u But, sp 2 Terminal CH with hybridized carbon atoms 2 There is a condition that the group is not included.

[0051] Preferably, R u is represented by formula (XII): [ka] (wherein the dashed bond represents the carbonyl carbon ( * ) showing a bond to the aryl group.

[0052] R u When is an organic group having the formula (XII), the ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester.

[0053] R 5 ~R 8 are each independently a hydrogen atom or an organic group having 1 to 70 carbon atoms.

[0054] In a preferred method of the present invention, R 5 ~R 8 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 2~70 -alkynyl, substituted or unsubstituted C 1~70 -heteroalkyl, substituted or unsubstituted C 3~70 -cycloalkyl, substituted or unsubstituted C 3~70 -cycloalkenyl, substituted or unsubstituted C 2~70 -heterocycloalkyl, substituted or unsubstituted C 6~70 -aryl and substituted or unsubstituted C 4~70 -heteroaryl, preferably substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, substituted or unsubstituted C 2~50-alkynyl, substituted or unsubstituted C 1~50 -heteroalkyl, substituted or unsubstituted C 3~50 -cycloalkyl, substituted or unsubstituted C 3~50 -cycloalkenyl, substituted or unsubstituted C 2~50 -heterocycloalkyl, substituted or unsubstituted C 6~50 -aryl, and substituted or unsubstituted C 4~50 -heteroaryl, more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, substituted or unsubstituted C 2~30 -alkynyl, substituted or unsubstituted C 1~30 -heteroalkyl, substituted or unsubstituted C 3~30 -cycloalkyl, substituted or unsubstituted C 3~30 -cycloalkenyl, substituted or unsubstituted C 2~30 -heterocycloalkyl, substituted or unsubstituted C 6~30 -aryl, and substituted or unsubstituted C 4~30 -heteroaryl, even more preferably substituted or unsubstituted C 1~20 -Alkyl (e.g., C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), substituted or unsubstituted C 2~20 -Alkynyl (e.g., C 8~20 -alkynyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 3~20 -Cycloalkyl (e.g. C 8~20 -cycloalkyl), substituted or unsubstituted C 3~20 -Cycloalkenyl (e.g., C 8~20 -cycloalkenyl), substituted or unsubstituted C 2~20 -heterocycloalkyl (e.g., C 8~20 -heterocycloalkyl), substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g. C8~20 -heteroaryl). Preferably, R 5 ~R 8 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 1~70 -heteroalkyl, substituted or unsubstituted C 6~70 -aryl, and substituted or unsubstituted C 4~70 -heteroaryl, more preferably substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, substituted or unsubstituted C 1~50 -heteroalkyl, substituted or unsubstituted C 6~50 -aryl, and substituted or unsubstituted C 4~50 -heteroaryl, even more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, substituted or unsubstituted C 1~30 -heteroalkyl, substituted or unsubstituted C 6~30 -aryl, and substituted or unsubstituted C 4~30 -heteroaryl, even more preferably substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g. C 8~20 -heteroaryl). More preferably, R 5 ~R 8 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, and substituted or unsubstituted C 6~70-aryl, more preferably a hydrogen atom, a substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, and substituted or unsubstituted C 6~50 -aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, and substituted or unsubstituted C 6~30 -aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), and substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl). More preferably, R 5 ~R 8 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -Alkyl and substituted or unsubstituted C 6~70 -aryl, more preferably a hydrogen atom, a substituted or unsubstituted C 1~50 -Alkyl and substituted or unsubstituted C 6~50- aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~30 -Alkyl and substituted or unsubstituted C 6~30 -aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl) and substituted or unsubstituted C 6~20- Aryl (e.g., C 8~20- aryl). Even more preferably, R 5 ~R 8 are each independently selected from hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. 5 ~R 8is a hydrogen atom; or R 5 , R 6 and R 7 Two of these, or R 6 , R 7 , and R 8 Two of them, together with the atoms to which they are attached, form a substituted or unsubstituted cycloalkyl ring, a substituted or unsubstituted cycloalkenyl ring, or a substituted or unsubstituted heterocycloalkyl ring, such as an alkylcyclohex-2-ene-1-carboxylate or an alkylcyclopentene-1-carboxylate.

[0055] R 9 is H or an organic group having 1 to 70 carbon atoms. 9 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 2~70 -alkynyl, substituted or unsubstituted C 1~70 -heteroalkyl, substituted or unsubstituted C 3~70 -cycloalkyl, substituted or unsubstituted C 3~70 -cycloalkenyl, substituted or unsubstituted C 2~70 -heterocycloalkyl, substituted or unsubstituted C 6~70 -aryl, and substituted or unsubstituted C 4~70 -heteroaryl, preferably H, substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, substituted or unsubstituted C 2~50 -alkynyl, substituted or unsubstituted C 1~50 -heteroalkyl, substituted or unsubstituted C 3~50 -cycloalkyl, substituted or unsubstituted C 3~50 -cycloalkenyl, substituted or unsubstituted C 2~50 -heterocycloalkyl, substituted or unsubstituted C 6~50 -aryl, and substituted or unsubstituted C 4~50 -heteroaryl, more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30-alkenyl, substituted or unsubstituted C 2~30 -alkynyl, substituted or unsubstituted C 1~30 -heteroalkyl, substituted or unsubstituted C 3~30 -cycloalkyl, substituted or unsubstituted C 3~30 -cycloalkenyl, substituted or unsubstituted C 2~30 -heterocycloalkyl, substituted or unsubstituted C 6~30 -aryl, and substituted or unsubstituted C 4~30 -heteroaryl, even more preferably H, substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), substituted or unsubstituted C 2~20 -Alkynyl (e.g., C 8~20 -alkynyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 3~20 -Cycloalkyl (e.g. C 8~20 -cycloalkyl), substituted or unsubstituted C 3~20 -Cycloalkenyl (e.g., C 8~20 -cycloalkenyl), substituted or unsubstituted C 2~20 -heterocycloalkyl (e.g., C 8~20 -heterocycloalkyl), substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g. C 8~20 -heteroaryl). Preferably, R 9 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 1~70 -heteroalkyl, substituted or unsubstituted C 6~70 -aryl, and substituted or unsubstituted C 4~70 -heteroaryl, more preferably H, substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50-alkenyl, substituted or unsubstituted C 1~50 -heteroalkyl, substituted or unsubstituted C 6~50 -aryl, and substituted or unsubstituted C 4~50 -heteroaryl, even more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, substituted or unsubstituted C 1~30 -heteroalkyl, substituted or unsubstituted C 6~30 -aryl, and substituted or unsubstituted C 4~30 -heteroaryl, more preferably H, substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g. C 8~20 -heteroaryl). More preferably, R 9 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, and substituted or unsubstituted C 6~70- aryl, more preferably H, substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, and substituted or unsubstituted C 6~50- aryl, and even more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, and substituted or unsubstituted C 6~30- aryl, and even more preferably H, substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20-alkenyl), and substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl). More preferably, R 9 is H, substituted or unsubstituted C 1~70 -Alkyl and substituted or unsubstituted C 6~70 -aryl, more preferably H, substituted or unsubstituted C 1~50 -Alkyl and substituted or unsubstituted C 6~50- aryl, and even more preferably H, substituted or unsubstituted C 1~30 -Alkyl and substituted or unsubstituted C 6~30 -aryl, even more preferably H, substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl) and substituted or unsubstituted C 6~20- Aryl (e.g. C 8~20- aryl). Even more preferably, R 9 is selected from H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. 9 is selected from methyl, ethyl, and n-propyl.

[0056] Or, R u is represented by formula (XIII): [ka] (wherein the dashed bond represents the carbonyl carbon ( * ) showing a bond to the alkyl group.

[0057] R u When is an organic group of formula (XIII), the ester-containing substrate of formula (I) comprises a β,γ-unsaturated ester.

[0058] R 10 ~R 12are each independently a hydrogen atom or an organic group having 1 to 70 carbon atoms.

[0059] In a preferred method of the present invention, R 10 ~R 12 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 2~70 -alkynyl, substituted or unsubstituted C 1~70 -heteroalkyl, substituted or unsubstituted C 3~70 -cycloalkyl, substituted or unsubstituted C 3~70 -cycloalkenyl, substituted or unsubstituted C 2~70 -heterocycloalkyl, substituted or unsubstituted C 6~70 -aryl, and substituted or unsubstituted C 4~70 -heteroaryl, preferably substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, substituted or unsubstituted C 2~50 -alkynyl, substituted or unsubstituted C 1~50 -heteroalkyl, substituted or unsubstituted C 3~50 -cycloalkyl, substituted or unsubstituted C 3~50 -cycloalkenyl, substituted or unsubstituted C 2~50 -heterocycloalkyl, substituted or unsubstituted C 6~50 -aryl, and substituted or unsubstituted C 4~50 -heteroaryl, more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, substituted or unsubstituted C 2~30 -alkynyl, substituted or unsubstituted C 1~30 -heteroalkyl, substituted or unsubstituted C 3~30 -cycloalkyl, substituted or unsubstituted C 3~30 -cycloalkenyl, substituted or unsubstituted C 2~30 -heterocycloalkyl, substituted or unsubstituted C 6~30 -aryl, and substituted or unsubstituted C 4~30-heteroaryl, even more preferably substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), substituted or unsubstituted C 2~20 -Alkynyl (e.g., C 8~20 -alkynyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 3~20 -Cycloalkyl (e.g. C 8~20 -cycloalkyl), substituted or unsubstituted C 3~20 -Cycloalkenyl (e.g., C 8~20 -cycloalkenyl), substituted or unsubstituted C 2~20 -heterocycloalkyl (e.g., C 8~20 -heterocycloalkyl), substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g. C 8~20 -heteroaryl). Preferably, R 10 ~R 12 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 1~70 -heteroalkyl, substituted or unsubstituted C 6~70 -aryl, and substituted or unsubstituted C 4~70 -heteroaryl, more preferably substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, substituted or unsubstituted C 1~50 -heteroalkyl, substituted or unsubstituted C 6~50 -aryl, and substituted or unsubstituted C 4~50 -heteroaryl, even more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, substituted or unsubstituted C 1~30-heteroalkyl, substituted or unsubstituted C 6~30 -aryl, and substituted or unsubstituted C 4~30 -heteroaryl, even more preferably substituted or unsubstituted C 1~20 -(For example, C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl), and substituted or unsubstituted C 4~20 -heteroaryl (e.g. C 8~20 -heteroaryl). More preferably, R 10 ~R 12 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, and substituted or unsubstituted C 6~70 -aryl, more preferably a hydrogen atom, a substituted or unsubstituted C 1~50 -alkyl, substituted or unsubstituted C 2~50 -alkenyl, and substituted or unsubstituted C 6~50 -aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, and substituted or unsubstituted C 6~30 -aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), and substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 -aryl). More preferably, R 10 ~R 12 each independently represents a hydrogen atom, a substituted or unsubstituted C 1~70 -Alkyl and substituted or unsubstituted C6~70 -aryl, more preferably a hydrogen atom, a substituted or unsubstituted C 1~50 -Alkyl and substituted or unsubstituted C 6~50- aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~30 -Alkyl and substituted or unsubstituted C 6~30 -aryl, and even more preferably a hydrogen atom, a substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl) and substituted or unsubstituted C 6~20 -aryl (e.g. C 8~20 Even more preferably, R 10 ~R 12 are each independently selected from hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. 10 ~R 12 is a hydrogen atom; or R 10 , R 11 , and R 12 Two of them, together with the atom to which they are attached, form a substituted or unsubstituted cycloalkyl ring, a substituted or unsubstituted cycloalkenyl ring, or a substituted or unsubstituted heterocycloalkyl ring.

[0060] R 13 is H or an organic group having 1 to 70 carbon atoms. 13 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 2~70 -alkynyl, substituted or unsubstituted C 1~70 -heteroalkyl, substituted or unsubstituted C 3~70 -cycloalkyl, substituted or unsubstituted C 3~70 -cycloalkenyl, and substituted or unsubstituted C 2~70 -heterocycloalkyl, preferably H, substituted or unsubstituted C 1~50-alkyl, substituted or unsubstituted C 2~50 -alkenyl, substituted or unsubstituted C 2~50 -alkynyl, substituted or unsubstituted C 1~50 -heteroalkyl, substituted or unsubstituted C 3~50 -cycloalkyl, substituted or unsubstituted C 3~50 -cycloalkenyl, and substituted or unsubstituted C 2~50 -heterocycloalkyl, more preferably H, substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, substituted or unsubstituted C 2~30 -alkynyl, substituted or unsubstituted C 1~30 -heteroalkyl, substituted or unsubstituted C 3~30 -cycloalkyl, substituted or unsubstituted C 3~30 -cycloalkenyl, and substituted or unsubstituted C 2~30 -heterocycloalkyl, even more preferably H, substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), substituted or unsubstituted C 2~20 -Alkynyl (e.g., C 8~20 -alkynyl), substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl), substituted or unsubstituted C 3~20 -Cycloalkyl (e.g. C 8~20 -cycloalkyl), substituted or unsubstituted C 3~20 -Cycloalkenyl (e.g., C 8~20 -cycloalkenyl), and substituted or unsubstituted C 2~20 -heterocycloalkyl (e.g., C 8~20 -heterocycloalkyl). Preferably, R 13 is H, substituted or unsubstituted C 1~70 -alkyl, and substituted or unsubstituted C 2~70 -alkenyl, substituted or unsubstituted C 1~70 -heteroalkyl, more preferably H, substituted or unsubstituted C 1~50-alkyl, substituted or unsubstituted C 2~50 -alkenyl, and substituted or unsubstituted C 1~50 -heteroalkyl, even more preferably substituted or unsubstituted C 1~30 -alkyl, substituted or unsubstituted C 2~30 -alkenyl, and substituted or unsubstituted C 1~30 -heteroalkyl, even more preferably H, substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl), and substituted or unsubstituted C 1~20 -heteroalkyl (e.g., C 8~20 -heteroalkyl). More preferably, R 13 is H, substituted or unsubstituted C 1~70 -alkyl, substituted or unsubstituted C 2~70 -alkenyl, and substituted or unsubstituted C 6~70- aryl, more preferably H, substituted or unsubstituted C 1~50 -alkyl, and substituted or unsubstituted C 2~50 -alkenyl, and even more preferably H, substituted or unsubstituted C 1~30 -alkyl, and substituted or unsubstituted C 2~30- alkenyl, and even more preferably substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 -alkyl), and substituted or unsubstituted C 2~20 -Alkenyl (e.g., C 8~20 -alkenyl). More preferably, R 13 is H, substituted or unsubstituted C 1~70 -alkyl, more preferably substituted or unsubstituted C 1~50 -alkyl, and even more preferably H, substituted or unsubstituted C 1~30 -alkyl, and even more preferably substituted or unsubstituted C 1~20 -Alkyl (e.g. C 8~20 Even more preferably, R 13is selected from H, methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, phenyl, tolyl, xylyl, and methoxyphenyl. 13 is selected from methyl, ethyl, and n-propyl.

[0061] R 13 But, sp 2 Terminal CH with hybridized carbon atoms 2 In some cases, it may be preferable that the R 9 But, sp 2 Terminal CH with hybridized carbon atoms 2 In some cases, it may be preferable that the R 9 and R 13 But, sp 2 Terminal CH with hybridized carbon atoms 2 In some cases, it may be preferable that the aryl group is not a group.

[0062] In the ester-containing substrate of formula (I), R v is an organic group having 1 to 70 carbon atoms. In a preferred method of the present invention, R v is a substituted or unsubstituted C 1~70 -alkyl, preferably substituted or unsubstituted C 1~50 -alkyl, more preferably substituted or unsubstituted C 1~30 -alkyl, even more preferably substituted or unsubstituted C 1~20 -Alkyl (e.g., C 2~20 -Alkyl or C 3~20 -alkyl). Preferably, R v is a substituted or unsubstituted C 2~70 -alkyl, more preferably substituted or unsubstituted C 2~50 -alkyl, even more preferably substituted or unsubstituted C 2~30 -alkyl, even more preferably substituted or unsubstituted C 1~20 -Alkyl, C 2~20 -alkyl, or C 3~20 -alkyl. More preferably, R vis selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, pentyl, hexyl, heptyl, and octyl. More preferably, R v is selected from methyl, ethyl, n-propyl, or iso-propyl. Even more preferably, R v is ethyl, n-butyl, or tert-butyl. Most preferably, R v is ethyl.

[0063] In a preferred method of the present invention, the ester-containing substrate of formula (I) is an alkyl sorbate. Preferably, the alkyl sorbate is methyl sorbate, ethyl sorbate, n-propyl sorbate, iso-propyl sorbate, n-butyl sorbate, sec-butyl sorbate, or tert-butyl sorbate. More preferably, the alkyl sorbate is methyl sorbate or ethyl sorbate.

[0064] In a preferred method of the present invention, the ester-containing substrate of formula (I) is an alkyl trans-3-hexanoate. Preferably, the alkyl trans-3-hexanoate is methyl trans-3-hexanoate, ethyl trans-3-hexanoate, n-propyl trans-3-hexanoate, isopropyl trans-3-hexanoate, n-butyl trans-3-hexanoate, sec-butyl trans-3-hexanoate, iso-butyl trans-3-hexanoate, or tert-butyl trans-3-hexanoate. More preferably, the alkyl trans-3-hexanoate is methyl trans-3-hexanoate or ethyl trans-3-hexanoate.

[0065] In a preferred method of the present invention, the ester-containing substrate of formula (I) is an alkyl cis-3-hexanoate. Preferably, the alkyl cis-3-hexanoate is methyl cis-3-hexanoate, ethyl cis-3-hexanoate, n-propyl cis-3-hexanoate, iso-propyl cis-3-hexanoate, n-butyl cis-3-hexanoate, sec-butyl cis-3-hexanoate, iso-butyl cis-3-hexanoate, or tert-butyl cis-3-hexanoate. More preferably, the alkyl cis-3-hexanoate is methyl cis-3-hexanoate or ethyl cis-3-hexanoate.

[0066] In a preferred method of the invention, the ester-containing substrate of formula (I) is an alkyl sorbate, an alkyl trans-3-hexanoate, or an alkyl cis-3-hexanoate as defined above.

[0067] Alcohol Products When the ester-containing substrate of formula (I) is a monoester, the product of the process of the invention is an alcohol of formula (II). In a preferred process of the invention, the group R u The configuration of the alkenyl group in is the same in the ester-containing substrate of formula (I) and the product alcohol of formula (II).

[0068] In a preferred process of the invention, the alcohol of formula (II) is trans,transhexa-2,4-dien-1-ol: [ka] It is.

[0069] Thus, in a preferred embodiment of the present invention, the process is a process for hydrogenating an ester-containing substrate of formula (I) to produce an alcohol of formula (II), which is trans,trans-hexa-2,4-dien-1-ol.

[0070] In the most preferred method of the present invention, the ester-containing substrate of formula (I) is an alkyl sorbate as defined above and the alcohol of formula (II) is trans,trans-hexa-2,4-dien-1-ol.

[0071] In a preferred process of the invention, the alcohol of formula (II) is trans-hex-3-en-1-ol: [ka] It is.

[0072] Thus, in a preferred embodiment of the invention, the process is a process for hydrogenating an ester-containing substrate of formula (I) to produce an alcohol of formula (II), which is trans-hex-3-en-1-ol.

[0073] In the most preferred process of the present invention, the ester-containing substrate of formula (I) is an alkyl trans-3-hexanoate as defined above and the alcohol of formula (II) is trans-hex-3-en-1-ol.

[0074] In a preferred process of the invention, the alcohol of formula (II) is cis-hex-3-en-1-ol: [ka] It is.

[0075] Thus, in a preferred embodiment of the invention, the process is a process for hydrogenating an ester-containing substrate of formula (I) to produce an alcohol of formula (II), which is cis-hex-3-en-1-ol.

[0076] In the most preferred process of the present invention, the ester-containing substrate of formula (I) is an alkyl cis-3-hexanoate as defined above and the alcohol of formula (II) is cis-hex-3-en-1-ol.

[0077] base The bases of the present invention are those whose conjugate acids have a pKa of 4-15. Without wishing to be bound by any theory, it is believed that the use of bases whose conjugate acids have a pKa of 4-15 minimizes or prevents the formation of enolate intermediates in the hydrogenation process of the present invention. It is speculated that the formation of such enolate intermediates may be responsible for the reduction of the alkenyl functionality and the loss of regiochemistry of the alkene. It is further believed that the formation of enolate intermediates may cause the formation of other undesirable by-products, such as those resulting from cycloaddition reactions (e.g., Diels-Alder) or condensation reactions. Furthermore, it is believed that the base plays a role in activating the transition metal catalyst. It is therefore surprising that a base whose conjugate acid has a pKa of 4-15 functions to activate the transition metal catalyst of the present invention while simultaneously minimizing or preventing the formation of enolate intermediates.

[0078] In preferred methods of the invention, the conjugate acid of the base has a pKa greater than 5, greater than 7, or greater than 9. In preferred methods of the invention, the conjugate acid of the base has a pKa less than 14, less than 13, or less than 12. In preferred methods of the invention, the conjugate acid of the base has a pKa between 5 and 14, between 7 and 13, or between 9 and 12, such as between 9 and 11, for example about 10.

[0079] In a preferred method of the invention, the base is a metal phosphate or metal carbonate, and the conjugate acid of the base has a pKa of 4 to 15. The metal carbonate or metal phosphate is preferably an alkali metal phosphate, an alkaline earth metal phosphate, an alkali metal carbonate, or an alkaline earth metal carbonate, and the conjugate acid of the base has a pKa of 4 to 15.

[0080] In a more preferred method of the present invention, the base is a metal phosphate, the conjugate acid of which has a pKa of 4 to 15. The metal phosphate is preferably an alkali metal phosphate or an alkaline earth metal phosphate, the conjugate acid of which has a pKa of 4 to 15. The metal phosphate is more preferably an alkali metal phosphate. The alkali metal phosphate is preferably lithium phosphate (Li3 PO 4 ), Sodium phosphate (Na 3 PO 4 ), potassium phosphate (K 3 PO 4 ), or cesium phosphate (Cs 3 PO 4 ). Most preferably, the base is potassium phosphate (K 3 PO 4 ) is an alkali metal phosphate.

[0081] In a preferred process of the invention, the base is present in solid form.

[0082] In a preferred process of the invention, the base is present in at least 30 mol % based on the total amount of ester-containing substrates, preferably at least 35 mol % based on the total amount of ester-containing substrates, more preferably at least 40 mol % based on the total amount of ester-containing substrates, even more preferably at least 45 mol % based on the total amount of ester-containing substrates.

[0083] In preferred processes of the invention, the base is present in an amount of no more than 200 mole % based on the total amount of ester-containing substrate, more preferably no more than 125 mole % based on the total amount of ester-containing substrate.

[0084] In a preferred process of the invention, the base is present in the range of 30-70 mol % based on the total amount of ester-containing substrate, more preferably in the range of 30-60 mol % based on the total amount of ester-containing substrate, even more preferably in the range of 30-50 mol % based on the total amount of ester-containing substrate.

[0085] In a preferred method of the present invention, the base is present as a solid in the method. In a preferred method of the present invention, the base is substantially insoluble in the ester-containing substrate of formula (I) and / or the alcohol of formula (II). In a preferred method of the present invention, the base is substantially insoluble in the solvent.

[0086] In a preferred process of the invention, the process further comprises the step of separating the base by filtration. The post-filtration step of separating the base is carried out after hydrogenation of the ester-containing substrate of formula (I).

[0087] The use of a base that is substantially insoluble in the ester-containing substrate of formula (I) and / or the alcohol and / or solvent of formula (II) has the advantage that it can be easily separated from the reaction product, e.g., from the alcohol of formula (II). Thus, potassium phosphate (K phosphate), which is insoluble in organic solvents such as toluene and THF, is preferred. 3 PO 4 ) have the added advantage that they are easy to separate, for example by filtration.

[0088] solvent In a preferred process of the invention, the process is carried out in the absence of a solvent, which has the advantage that it makes the process easier and cheaper to carry out.

[0089] In another preferred process of the present invention, the process is carried out in the presence of a solvent.

[0090] Preferably, the solvent is selected from alcohol, toluene, THF and Me-THF. More preferably, the solvent is selected from toluene, THF and Me-THF. Most preferably, the solvent is selected from toluene and THF.

[0091] In a preferred method of the invention, the solvent is present in an amount of 10 to 100% by volume based on the total volume of the ester-containing substrate, preferably 15 to 95% by volume based on the total volume of the ester-containing substrate, more preferably 20 to 90% by volume based on the total volume of the ester-containing substrate (e.g., 50% by volume based on the total volume of the ester-containing substrate).

[0092] In a preferred process of the invention, the volume ratio of solvent to ester-containing substrate is no more than 1:1, preferably no more than 1:2.

[0093] In a preferred process of the present invention, the volume ratio of the solvent to the ester-containing substrate is in the range of 1:2 to 1:1, preferably in the range of 1:2 to 1:1.5.

[0094] In a preferred process of the invention, the process is carried out in the presence of two or more solvents. Preferred solvents are as described above.

[0095] In another preferred process of the present invention, the process is carried out in the presence of a first solvent and a second solvent.

[0096] In a preferred process of the invention, the first solvent is selected from toluene, THF and Me-THF. In a preferred process of the invention, the second solvent is an alcohol, preferably methanol or ethanol.

[0097] In a particularly preferred process of the invention, the first solvent is toluene and the second solvent is an alcohol, preferably methanol or ethanol.

[0098] In an alternative particularly preferred process of the invention, the first solvent is THF and the second solvent is an alcohol, preferably methanol or ethanol.

[0099] In a preferred method of the invention, the first solvent is present in an amount of 10 to 100% by volume based on the total volume of the ester-containing substrate, preferably 15 to 95% by volume based on the total volume of the ester-containing substrate, more preferably 20 to 90% by volume based on the total volume of the ester-containing substrate (e.g., 50% by volume based on the total volume of the ester-containing substrate).

[0100] In a preferred method of the invention, the volume ratio of the first solvent to the ester-containing substrate is no more than 1:1, preferably no more than 1:2.

[0101] In a preferred method of the present invention, the volume ratio of the first solvent to the ester-containing substrate is in the range of 1:2 to 1:1, preferably in the range of 1:2 to 1:1.5.

[0102] In a preferred method of the invention, the second solvent is present in an amount of 1-15% by volume based on the total volume of the ester-containing substrate, preferably in an amount of 1-10% by volume based on the total volume of the ester-containing substrate, preferably in an amount of 1-7.5% by volume based on the total volume of the ester-containing substrate, more preferably in an amount of 1-5% by volume based on the total volume of the ester-containing substrate.

[0103] In a preferred method of the present invention, the first solvent is present in an amount of 10-100% by volume based on the total volume of the ester-containing substrate and the second solvent is present in an amount of 1-10% by volume based on the total volume of the ester-containing substrate; preferably, the first solvent is present in an amount of 15-95% by volume based on the total volume of the ester-containing substrate and the second solvent is present in an amount of 1-7.5% by volume based on the total volume of the ester-containing substrate; more preferably, the first solvent is present in an amount of 20-90% by volume based on the total volume of the ester-containing substrate and the second solvent is present in an amount of 1-5% by volume based on the total volume of the ester-containing substrate.

[0104] by-product The process of the present invention has the surprising advantage of producing less unwanted by-products.

[0105] As discussed above, prior art processes and / or processes in which strong bases (eg, those whose conjugate acids have a pKa greater than 15, such as metal alkoxides) are used can result in the formation of unwanted by-products.

[0106] Unwanted by-products typically include wax esters, saturated alcohols, saturated esters, and hemiacetals. Without wishing to be bound by any theory, it is believed that the formation of these unwanted by-products is due to the formation of enolate intermediate compounds. Therefore, it is believed that the method of the present invention minimizes or eliminates the formation of enolate intermediates, and therefore forms less unwanted by-products.

[0107] temperature The process of the present invention may be carried out at a temperature in the range of 20 to 150° C. In a preferred process of the present invention, the process may be carried out at a temperature in the range of 40 to 90° C., more preferably in the range of 40 to 85° C., even more preferably in the range of 50 to 85° C., even more preferably in the range of 50 to 80° C., even more preferably in the range of 55 to 75° C., and most preferably in the range of 60 to 75° C. (e.g., about 70° C.).

[0108] The preferred process of the present invention is carried out at relatively low temperatures. It has surprisingly been found that the use of temperatures within the preferred ranges described above results in less production of undesirable by-products than does the use of higher temperatures, while still maintaining good reaction rates.

[0109] In a particularly preferred embodiment of the process, the solvent is toluene and the process is carried out at a temperature in the range of 40 to 90°C, more preferably in the range of 45 to 85°C, even more preferably in the range of 50 to 85°C, even more preferably in the range of 50 to 80°C, even more preferably in the range of 55 to 75°C, most preferably in the range of 60 to 75°C (e.g. about 70°C).

[0110] When toluene is the solvent, it is surprising that temperatures below the atmospheric boiling point of toluene (about 110° C.) improve hydrogen gas uptake in the hydrogenation process.

[0111] pressure Preferred processes of the invention are carried out at a pressure of at least 5 bar, more preferably at least 10 bar, even more preferably at least 20 bar, even more preferably at least 30 bar, even more preferably at least 40 bar and most preferably at least 50 bar.

[0112] Preferred processes of the present invention are carried out at pressures in the range of from 5 to 100 bar, more preferably in the range of from 10 to 95 bar, even more preferably in the range of from 20 to 90 bar, even more preferably in the range of from 25 to 70 bar and most preferably in the range of from 30 to 50 bar.

[0113] Duration A preferred process of the present invention is carried out for a period of from 1 to 24 hours, more preferably from 2 to 20 hours, even more preferably from 3 to 18 hours, and most preferably from 4 to 16 hours.

[0114] S / C-substrate / catalyst In a preferred method of the present invention, the substrate / catalyst loading is 500 / 1 or more, preferably 650 / 1 or more, more preferably 750 / 1 or more, even more preferably 850 / 1 or more. In a preferred method of the present invention, the substrate / catalyst loading is 50,000 / 1 or less, preferably 30,000 / 1 or less, more preferably 20,000 / 1 or less, even more preferably 10,000 / 1 or less. For example, in a preferred method of the present invention, the substrate / catalyst loading is 500 / 1 or more and 50,000 / 1 or less, preferably 650 / 1 or more and 30,000 / 1 or less, more preferably 750 / 1 or more and 20,000 / 1 or less, even more preferably 1,000 / 1 or more and 10,000 / 1 or less, for example 5,000 / 1.

[0115] transition metal catalyst The process of the present invention uses a transition metal catalyst. The transition metal catalyst may be preformed or may be formed in situ during the ester hydrogenation reaction. Preferably, the transition metal catalyst is preformed. Alternatively, the transition metal catalyst is formed in situ during the ester hydrogenation reaction.

[0116] In a preferred method of the invention, the transition metal in the transition metal catalyst is a transition metal of Group 6, Group 7, Group 8, or Group 9. More preferably, the transition metal in the transition metal catalyst is a transition metal of Group 7, Group 8, or Group 9. Even more preferably, the transition metal in the transition metal catalyst is a transition metal of Group 8.

[0117] In a preferred process of the present invention, the transition metal in the transition metal catalyst is selected from Mo, Mn, Fe, Ru, Co and Os. More preferably, the transition metal in the transition metal catalyst is selected from Ru and Os. Most preferably, the transition metal in the transition metal catalyst is Ru.

[0118] In a preferred process of the invention, the transition metal catalyst used in the process of the invention comprises a tridentate ligand.

[0119] In a preferred process of the present invention, the transition metal catalyst comprises a tridentate ligand having the formula (III) [ka] (In the formula, X is -SR a , -OR a , -CR a , -NR a R b , -PR a R b , -P(=O)R a R b , -OPR a R b , and -NHPR a R b Selected from; R 1 and R x each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20- Heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl, or R 1 and R 3a and R 3bEither of or R x and R 3a and R 3b form a ring together with the atoms to which they are attached; Alternatively, X is a heteroatom and R x If does not exist, R 1 together with form an optionally substituted heterocycle; Y is -SR a , -OR a , -CR a , -NR a R b , -PR a R b , -P(=O)R a R b , -OPR a R b , and -NHPR a R b Selected from; R 2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl, or R 2 and R 4a and R 4b Either of or R y and R 4a and R 4b form a ring with the atoms to which they are attached; Alternatively, Y is a heteroatom and R y If does not exist, R 2 together with form an optionally substituted heterocycle; R 3a、 R 3b , R 4a and R 4b each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl, or R 3a and R 4a and R 4b Either of or R 3b and R 4a and R 4b together with the atoms to which they are attached form a heterocycle; R 5 is hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; each m and n is independently 1 or 2; and R a and R b each independently, if present, is hydrogen, substituted or unsubstituted C 1~20-alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or X and / or Y are selected from -NR a R b , -PR a R b , -OPR a R b , or -NHPR a R b If R a and R b form a heterocycle together with the heteroatom to which they are attached.

[0120] In the tridentate ligand of formula (III), X is preferably -SR a , -CR a , -NR a R b , -PR a R b , and -NHPR a R b More preferably, X is selected from -SR a , -PR a R b , and -NHPR a R b Even more preferably, X is selected from -SR a and -PR a R b Most preferably, X is selected from -SR a It is.

[0121] In the tridentate ligand of formula (III), R 1 and R xare each independently preferably hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20- Heteroalkyl, and substituted or unsubstituted C 3~20- More preferably, R 1 and R x are each independently hydrogen and substituted or unsubstituted C 1~20 Even more preferably, R 1 and R x are hydrogen.

[0122] In another preferred tridentate ligand of formula (III), R x is absent, X is a heteroatom, and R 1 and together form an optionally substituted heterocycle. More preferably, R x is absent, X is a heteroatom, and R 1 and together form an optionally substituted heteroaromatic ring. More preferably, the optionally substituted heteroaromatic ring is an optionally substituted nitrogen-containing heteroaromatic ring. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl. Most preferably, the optionally substituted nitrogen-containing heteroaromatic ring is pyridinyl.

[0123] In the tridentate ligand of formula (III), Y is preferably -SR a , -CR a , -NR a R b , -PR a R b , and -NHPRa R b More preferably, Y is selected from -SR a , -PR a R b , and -NHPR a R b Even more preferably, Y is selected from -SR a and -PR a R b Most preferably, Y is selected from -SR a It is.

[0124] In the tridentate ligand of formula (III), R 2 and R y are each independently preferably hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl. More preferably, R 2 and R y each independently represents hydrogen and a substituted or unsubstituted C 1~20 Even more preferably, R 2 and R y are hydrogen.

[0125] In another preferred tridentate ligand of formula (III), Y is a heteroatom and R y If does not exist, R 2 and together form an optionally substituted heterocycle. More preferably, Y is a heteroatom and R y If does not exist, R 2and together form an optionally substituted heteroaromatic ring. More preferably, the optionally substituted heteroaromatic ring is an optionally substituted nitrogen-containing heteroaromatic ring. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl. Even more preferably, the optionally substituted nitrogen-containing heteroaromatic ring is selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl. Most preferably, the optionally substituted nitrogen-containing heteroaromatic ring is pyridinyl.

[0126] In the tridentate ligand of formula (III), R 3a , R 3b , R 4a , and R 4b are each independently preferably hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl. More preferably, R 3a , R 3b , R 4a , and R 4b each independently represents hydrogen and a substituted or unsubstituted C 1~20 Even more preferably, R 3a , R 3b , R 4a , and R 4b are hydrogen.

[0127] In another preferred tridentate ligand of formula (III), R 3a and R 4a and R 4b Either of or R 3b and R 4a and R 4btogether with the atoms to which they are attached form a heterocycle. Preferably, the heterocycle is a 6-membered heterocycle.

[0128] In the tridentate ligand of formula (III), R 5 is preferably hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl. More preferably, R 5 is hydrogen and substituted or unsubstituted C 1~20 Even more preferably, R 5 is hydrogen.

[0129] In the tridentate ligand of formula (III), each m and n is preferably 1.

[0130] In the tridentate ligand of formula (III), R a and R b are, when present, each independently preferably hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl. More preferably, R a and R b each independently, if present, is hydrogen, substituted or unsubstituted C 1~20 -Alkyl (e.g. C 1~10 -alkyl) and substituted or unsubstituted C 6~20 -aryl. Particularly preferred are C 1~20 Preferred C alkyl groups include ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, pentyl and hexyl, more preferably methyl, ethyl, iso-propyl, tert-butyl, and even more preferably ethyl. 6~20-Aryl groups include phenyl, tolyl, xylyl and methoxyphenyl, more preferably phenyl.

[0131] In another preferred tridentate ligand of formula (III), X and / or Y are -NR a R b , -PR a R b , -OPR a R b or -NHPR a R b If R a and R b form a heterocycle together with the heteroatom to which they are attached.

[0132] In a preferred process of the invention, the transition metal catalyst comprises a tridentate ligand having the formula (III): During the ceremony, X is -SR a , -CR a , -NR a R b , -PR a R b , and -NHPR a R b Selected from; R 1 and R x each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; Or X is a heteroatom, and R x If does not exist, R 1together with Y is -SR a , -CR a , -NR a R b , -PR a R b , and -NHPR a R b Selected from; R 2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or Y is a heteroatom, and R y If does not exist, R 2 together with R 3a , R 3b , R 4a , R 4b and R 5 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20-cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; each m and n is independently 1 or 2; and R a and R b each independently, if present, is hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or X and / or Y are selected from -NR a R b , -PR a R b or -NHPR a R b If R a and R b form a heterocycle together with the heteroatom to which they are attached.

[0133] In a preferred process of the invention, the transition metal catalyst comprises a tridentate ligand having the formula (III): During the ceremony, X is -SR a , -PR a R b , and -NHPR a R b Selected from; R 1 and R x each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20-alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; Or X is a heteroatom, R x If does not exist, R 1 together form an optionally substituted heteroaromatic ring which is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl; Y is -SR a , -PR a R b , and -NHPR a R b Selected from; R 2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or Y is a heteroatom, and R y If does not exist, R 2 together with - to form an optionally substituted heteroaromatic ring, the heteroaromatic ring being a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl; R 3a , R 3b , R 4a , R 4b and R 5 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; each m and n is independently 1 or 2; and R a and R b each independently, if present, is hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20-heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or X and / or Y are selected from -PR a R b or -NHPR a R b If R a and R b form a heterocycle together with the heteroatom to which they are attached.

[0134] In a preferred process of the invention, the transition metal catalyst comprises a tridentate ligand having the formula (III): During the ceremony, X is -SR a and -PR a R b Selected from; R 1 and R x each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; Or X is a heteroatom, and R x If does not exist, R 1 together with - to form an optionally substituted heteroaromatic ring, the heteroaromatic ring being a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl; Y is -SR a and -PR a R b Selected from; R 2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or Y is a heteroatom, and R y If does not exist, R 2 together with, form an optionally substituted heteroaromatic ring, the heteroaromatic ring being a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl; R 3a , R 3b , R 4a , R 4b and R 5 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; each m and n is independently 1 or 2; and Ra and R b each independently, if present, is hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or X and / or Y are selected from -PR a R b If R a and R b form a heterocycle together with the heteroatom to which they are attached.

[0135] In a preferred process of the invention, the transition metal catalyst comprises a tridentate ligand having formula (III): X is -SR a and; R 1 and R x each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; Y is -SR a and; R2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; R 3a , R 3b , R 4a , R 4b and R 5 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; each m and n is independently 1 or 2; and R a each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl.

[0136] Preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): During the ceremony, X is -SR a and; R 1 and R x each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl; Y is -SR a and; R 2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl; R 3a , R 3b , R 4a , R 4b and R 5 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl; each m and n is independently 1 or 2; and R a each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl.

[0137] More preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X is -SR a and; R 1 and R x are each independently hydrogen and substituted or unsubstituted C 1~20 - alkyl; Y is -SR a and; R 2 and R y are each independently hydrogen and substituted or unsubstituted C 1~20 - alkyl; R 3a , R 3b , R 4a , R 4b and R 5 are each independently hydrogen and substituted or unsubstituted C 1~20 - alkyl; each m and n is independently 1 or 2; and R a are each independently hydrogen and substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl.

[0138] Even more preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X and Y are -SR a and; R 1 , R x , R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 are each hydrogen; m and n are each 1; and R a each independently represents a substituted or unsubstituted C1~20 -alkyl, preferably C 1~10 It is an alkyl.

[0139] Even more preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X and Y are each -SEt; R 1 , R x , R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 are each hydrogen; and m and n are each 1.

[0140] In another preferred method of the present invention, the transition metal catalyst comprises a tridentate ligand having formula (III): X is a heteroatom and R 1 Together with R x when absent, forms an optionally substituted heteroaromatic ring; Y is -PR a R b and; R 2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; R 3a , R 3b , R 4a , R4b and R 5 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; each m and n is independently 1 or 2; and R a and R b each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or R a and R b form a heterocycle together with the heteroatom to which they are attached.

[0141] Preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X is a nitrogen atom, R x If does not exist, R 1together with Y is -PR a R b and; R 2 and R y each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, and substituted or unsubstituted C 3~20 -cycloalkyl; R 3a , R 3b , R 4a , R 4b and R 5 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 3~20 -cycloalkyl; each m and n is independently 1 or 2; and R a and R b each independently represents a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl.

[0142] More preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X is a nitrogen atom, R x If does not exist, R 1together form an optionally substituted heteroaromatic ring which is a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, thiadiazolyl, oxadiazolyl, pyrimidyl, benzoxazolyl, benzthiazolyl, benzimidazolyl, indolyl, and quinolinyl; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 are each hydrogen; each m and n is 1; and R a and R b each independently represents a substituted or unsubstituted C 1~20 -Alkyl and substituted or unsubstituted C 6~20 -aryl.

[0143] Even more preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X is a nitrogen atom, R x If does not exist, R 1 together with, form an optionally substituted heteroaromatic ring, the heteroaromatic ring being a nitrogen-containing heteroaromatic ring selected from pyridinyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, and pyrimidyl; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b , and R 5 are each hydrogen; each m and n is 1; and R a and Rb are each independently selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, phenyl, tolyl, xylyl, and methoxyphenyl.

[0144] Even more preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X is a nitrogen atom, R x If does not exist, R 1 together with form an optionally substituted pyridinyl ring; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 are each hydrogen; each m and n is 1; and R a and R b are each independently selected from methyl, ethyl, isopropyl, tert-butyl, phenyl, tolyl, xylyl, and methoxyphenyl.

[0145] Even more preferably, the transition metal catalyst comprises a tridentate ligand having the formula (III): X is a nitrogen atom, R x If does not exist, R 1 together with form an optionally substituted pyridinyl ring; Y is -PR a R b and; R 2 , R y , R 3a , R 3b , R 4a , R 4b and R 5 are each hydrogen; each m and n is 1; and R aand R b are each phenyl.

[0146] In a preferred process of the invention, the transition metal catalyst has formula (IV) or formula (V). [M(L 1 )(L 2 ) d ] (IV) [M(L 1 )(L 2 ) d ]W (V) (In the formula, M is a transition metal; L 1 is a tridentate ligand as defined herein; L 2 are ligands which may be the same or different; d is 1, 2 or 3; and W is a non-coordinating anionic ligand.

[0147] In a preferred method of the invention, M is a transition metal of Group 6, 7, 8 or 9. More preferably, M is a transition metal of Group 7, 8 or 9. Even more preferably, M is a transition metal of Group 8.

[0148] In a preferred method of the invention, M is a transition metal selected from Mo, Mn, Fe, Ru, Co and Os. More preferably, M is a transition metal selected from Ru and Os. Most preferably, M is Ru.

[0149] In a preferred method of the invention, d is 3.

[0150] As will be appreciated by those skilled in the art, each L 2 may be a monodentate or polydentate ligand, provided that L 2 Combinations of ligands are permitted by the valence rules. In a preferred method of the invention, each L 2 is a monodentate ligand. 2is independently a neutral monodentate ligand or an anionic monodentate ligand. In a preferred method of the invention, each L 2 are independently -H, -CO, -CN, -P(R') 3 , -As(R') 3 , -CR', -OR', -O(C=O)R', -NR' 2 , halogen (e.g., -Cl, -Br, -I), and solvent, where each R' is independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl. Preferably, each L 2 are independently -H, -CO, -P(R') 3 More preferably, each L is selected from 2 are independently -CO, -PPh 3 L is selected from -Cl. 2 When is the solvent, the solvent is preferably THF, Me-THF, MeCN, H 2 O, and alcohols (e.g., methanol, ethanol, isopropanol, etc.).

[0151] In the transition metal catalyst of formula (V), W is a non-coordinating anionic ligand. By "non-coordinating anionic ligand" is meant that the anionic ligand is forced to bind to the outer sphere of the metal center. Thus, the anionic ligand dissociates from the metal center. This is in contrast to neutral complexes where the anionic ligand binds to the metal within the coordination sphere. Anionic ligands can generally be identified as non-coordinating by analyzing the X-ray crystal structure of the cationic complex. Preferably, W is a triflate (i.e., TfO - or CF 3 SO 3 - ), tetrafluoroborate (i.e. -BF 4 ), hexafluoroantimonates (i.e. -SbF 6 ), hexafluorophosphate (PF6 - ), [B[3,5-(CF 3 ) 2 C 6 H 3 ] 4 ] - ([BArF 4 ] - ), halides (e.g., Cl - , Br - , I - ) and mesylate (MsO - or MeSO 3 - ).

[0152] Preferably, the transition metal catalyst is of formula (IV).

[0153] Alternatively, the transition metal catalyst is a transition metal catalyst of formula (V).

[0154] In a preferred method of the present invention, the transition metal catalyst is [ka] A transition metal catalyst selected from, for example, [ka] It is.

[0155] In a preferred method of the present invention, the transition metal catalyst is [ka] It is.

[0156] In a preferred method of the present invention, the transition metal catalyst is Ru-SNS, Ru-SNN, or Ru-PNN. More preferably, the transition metal catalyst is Ru-SNS or Ru-PNN.

[0157] In a preferred method of the present invention, the transition metal catalyst is [ka] It is.

[0158] In a preferred process of the invention, the transition metal catalyst used in the process of the invention comprises a bidentate ligand.

[0159] In a preferred process of the invention, the transition metal catalyst comprises a bidentate ligand having formula (VI). [ka] (In the formula, X' is -NHR ax and; Y' is -SR ax , -OR ax , -CR ax , -NR ax R bx , -PR ax R bx , -P(=O)R ax R bx , -OPR ax R bx , and -NHPR ax R bx Selected from; R 8a , R 8b , R 9a and R 9b each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; p is 1 or 2; and R ax and R bxeach independently, if present, is hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or X' and / or Y' are selected from -NR ax R bx , -PR ax R bx , -OPR ax R bx , or -NHPR ax R bx If R ax and R bx form a heterocycle together with the heteroatom to which they are attached.

[0160] In a preferred process of the present invention, the transition metal catalyst has formula (VII) or formula (VIII). [M(L 1 ) e (L 2 ) f ] (VII) [M(L 1 ) e (L 2 ) f ]W (VIII) (In the formula, M is a transition metal; L 1 are the bidentate ligands as described above, which may be the same or different; L 2 are ligands, if present, which may be the same or different; e is 1 or 2, and when e is 1, f is 2, 3, or 4, and when e is 2, f is 0, 1, or 2; and W is a non-coordinating anionic ligand. M, L 2 and W is generally as described above.

[0161] In a preferred process of the invention, the transition metal catalyst used in the process of the invention comprises a tetradentate ligand.

[0162] In a preferred process of the invention, the transition metal catalyst comprises a tetradentate ligand having the formula (IX). [ka] (In the formula, Q is -SR ay , -OR ay , -CR ay , -NR ay R by , -PR ay R by , -P(=O)R ay R by , -OPR ay R by , and -NHPR ay R by Selected from; R 15 and R q each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; Or Q is a heteroatom, Rq If does not exist, R 15 together with form an optionally substituted heterocycle; W is S, O, NR a , and PR a Selected from; R 16 , R w and R z each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or R 16 is R w If does not exist, R z together with form an optionally substituted heterocycle; Z is -SR ay , -OR ay , -CR ay , -NR ay R by , -PR ay R by , -P(=O)R ay R by , -OPR ay R by , and -NHPR ay R by Selected from; R 10a , R 10b , R 11a and R 11b each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or R 10a and R 11a and R 11b Either of or R 10b and R 11a and R 11b together with the atoms to which they are attached form a heterocycle; R 12a , R 12b , R 13a , R 13b and R 14 each independently represents hydrogen, a substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20 -alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; each q and r is independently 1 or 2; s is 0, 1 or 2; and R ay and R by each independently, if present, is hydrogen, substituted or unsubstituted C 1~20 -alkyl, substituted or unsubstituted C 2~20 -alkenyl, substituted or unsubstituted C 2~20-alkynyl, substituted or unsubstituted C 1~20 -heteroalkyl, substituted or unsubstituted C 1~20 -alkoxy, substituted or unsubstituted C 3~20 -cycloalkyl, substituted or unsubstituted C 3~20 -cycloalkenyl, substituted or unsubstituted C 2~20 -heterocycloalkyl, substituted or unsubstituted C 6~20 -aryl, and substituted or unsubstituted C 4~20 -heteroaryl; or Q and / or Z are -NR ay R by , -PR ay R by , -OPR ay R by , or -NHPR ay R by In the case of R ay and R by form a heterocycle together with the heteroatom to which they are attached.

[0163] In a preferred process of the present invention, the transition metal catalyst is represented by formula (X) or formula (XI) [M(L 1 )(L 2 ) g ] (X) [M(L 1 )(L 2 ) g ]W (XI) (In the formula, M is a transition metal; L 1 is a tetradentate ligand as defined herein; L 2 are ligands, if present, which may be the same or different; g is 0, 1 or 2; and W is a non-coordinating anionic ligand. M, L 2 and W is generally as described above.

[0164] In a preferred process of the invention, the transition metal catalyst is removed from the reaction mixture by a precipitation step using a co-solvent.

[0165] In another preferred process of the present invention, the transition metal catalyst is removed from the reaction mixture by distillation of the product.

[0166] In another preferred process of the present invention, the transition metal catalyst is removed from the reaction mixture by crystallization of the product.

[0167] In another preferred method of the present invention, the transition metal catalyst is removed from the reaction mixture using a metal scavenger.

[0168] In a preferred method of the invention, the process is a flow process. Preferably, the process is a flow process in which the excess base is recycled or reused. The base may be recycled or reused once, twice, three times or more.

[0169] The invention will now be further illustrated by the following non-limiting examples.

[0170] Working Example The catalysts Ru-SNS, Ru-PNN, SNS-RuHCl(CO), and PNN-RuHCl(CO) are commercially available from Johnson Matthey PLC and were used as supplied.

[0171] Ru-MACHO-BH is available from Strem Chemicals and was used as supplied.

[0172] OsPNN(N) is available from Merck and was used as supplied.

[0173] K 3 PO 4 and NaOEt are available from Acros Organics, Alfa Aesar, Fischer Scientific, and Merck. 3 PO 4were stored in an argon gas-filled glove box until use. Liquid reagents and anhydrous solvents were stored under nitrogen and transferred to reaction vials using standard air-sensitive handling procedures.

[0174] Reactions were carried out in a Biotage Endeavor multiwell pressurized reaction system using 10 mL reaction vials.

[0175] General Test Procedure The transition metal catalyst was added to the reaction vial along with the base in an argon-filled glove box. The anhydrous solvent was injected into the reaction vial followed by the substrate via syringe. The reactions were sealed in a Biotage Endeavour multi-well pressurized reaction system. The reaction vial was purged five times with nitrogen and once with hydrogen before being sealed and heated to the desired reaction temperature. The reaction vessel was pressurized to 400 psi with hydrogen and constantly stirred at 450-600 rpm. Each reaction was carried out for 16 hours. The reaction mixtures were analyzed by gas chromatography (GC) using ethanol as the solvent.

[0176] Measurement method Gas chromatography (GC) measurements were performed using a Varian 3900 or 3800 gas chromatograph system. Unless otherwise indicated, reaction conversions were determined by GC analysis.

[0177] Example 1: Hydrogenation of Esters The above general procedure can be carried out with an ester-containing substrate of formula (I): [ka] The study was carried out on the following subjects.

[0178] The desired product from substrate 1 and substrate 2 is the corresponding alcohol of formula (II), i.e.: [ka] It was.

[0179] The base may be a "weak base" according to the methods of the invention (e.g., K 3 PO 4 ) and a "strong base" not according to the method of the present invention (e.g., NaOEt, NaO t Bu).

[0180] Various reaction conditions were varied, including the amount of base (relative to substrate), substrate versus transition metal catalyst, reaction temperature, solvent system, and transition metal catalyst. The transition metal catalyst used in the examples is as defined above. Gas chromatographic analysis results show the conversion to the corresponding alcohol of formula (II), the molar amount of unreacted starting material, the molar amount of saturated starting material (i.e., where the starting material double bonds have been reduced but the ester has not), and the molar amount of waxy ester by-product. The experimental results are summarized in Tables 1-3 below. Examples 1-10 and 17-48 are in accordance with the present invention, while Examples 11-16 and 49-56 are comparative examples. [Table 1] [Table 2] [Table 3]

[0181] The examples show that the process of the present invention allows excellent conversion to the desired alcohol of formula (II) with minimal by-product formation, particularly low catalyst loadings can be used in a variety of solvent systems.

[0182] In contrast to the use of bases according to the invention, when "strong" bases such as NaOEt or NaotBu are used, conversion to the desired alcohol of formula (II) is incomplete, and instead by-products, such as those with reduced alkene linkages, those containing waxy ester materials, or other unidentified by-products, are formed.

Claims

1. A process for hydrogenating an ester-containing substrate of formula (I) to produce an alcohol of formula (II), comprising the steps of: 【Chemistry 1】 The method comprises treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen; The ester-containing substrate of formula (I) comprises an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester; R ｕ is an organic group having 3 to 70 carbon atoms, provided that R ｕ is the carbonyl carbon of the ester ( ＊ ) to form an α,β-γ,δ unsaturated ester or a β,γ unsaturated ester of formula (I); R ｖ is an organic group having 1 to 70 carbon atoms; and The conjugate acid of said base has a pKa of 4-15.

2. R ｕ is represented by formula (XII): 【Chemistry 2】 (wherein the dashed bond represents the carbonyl carbon ( ＊ ) and R ５ ~R ８ are each independently a hydrogen atom or an organic group having 1 to 70 carbon atoms; and R ９ The method of claim 1, wherein R is an organic group having H or an organic group having 1 to 70 carbon atoms.

3. R ｕ is represented by formula (XIII): 【Chemistry 3】 (wherein the dashed bond represents the carbonyl carbon ( ＊ ) and R １０ ~R １２ are each independently a hydrogen atom or an organic group having 1 to 70 carbon atoms; and R １３ The method of claim 1, wherein R is an organic group having H or an organic group having 1 to 70 carbon atoms.

4. R ｕ The method according to claim 1 , wherein is an organic group having the formula (XII) or an organic group having the formula (XIII) as defined in claim 2 or claim 3 .

5. 2. The method of claim 1, wherein the ester-containing substrate of formula (I) is an alkyl sorbate or an alkyl trans-3-hexanoate.

6. The method according to any one of claims 1 to 3 and 5, wherein the alcohol of formula (II) is trans,trans-hexa-2,4-dien-1-ol, cis-hex-3-en-1-ol, or trans-hex-3-en-1-ol.

7. The method of any one of claims 1 to 3 and 5, wherein the conjugate acid of the base has a pKa of 5 to 14, 7 to 13, or 9 to 12.

8. The method according to any one of claims 1 to 3 and 5, wherein the base is a metal phosphate or a metal carbonate.

9. The method according to any one of claims 1 to 3 and 5, wherein the base is an alkali metal phosphate, an alkaline earth metal phosphate, an alkali metal carbonate, or an alkaline earth metal carbonate.

10. The base is an alkali metal phosphate, preferably lithium phosphate (Li ３ P.O. ４ ), Sodium phosphate (Na ３ P.O. ４ ), potassium phosphate (K ３ P.O. ４ ), or cesium phosphate (Cs ３ P.O. ４ The method according to any one of claims 1 to 3 and 5, wherein

11. The method according to any one of claims 1 to 3 and 5, wherein the base is present in solid form.

12. 6. The method of claim 1, wherein the base is present in the range of 30 to 70 mol % based on the total amount of ester-containing substrate, in the range of 30 to 60 mol % based on the total amount of ester-containing substrate, or in the range of 30 to 50 mol % based on the total amount of ester-containing substrate.

13. The method of claim 1 , wherein the transition metal catalyst comprises a tridentate ligand.

14. The transition metal catalyst comprises a tridentate ligand having the formula (III): 【Chemistry 4】 (In the formula, X is -SR ａ , -OR ａ , -CR ａ , -NR ａ R ｂ , -PR ａ R ｂ , -P(=O)R ａ R ｂ , -OPR ａ R ｂ , and -NHPR ａ R ｂ Selected from: R １ and R ｘ are each independently hydrogen, substituted or unsubstituted C １～２０ - alkyl, substituted or unsubstituted C ２～２０ -alkenyl, substituted or unsubstituted C ２～２０ -alkynyl, substituted or unsubstituted C １～２０ -heteroalkyl, substituted or unsubstituted C １～２０ -alkoxy, substituted or unsubstituted C ３～２０ -cycloalkyl, substituted or unsubstituted C ３～２０ -cycloalkenyl, substituted or unsubstituted C ２～２０ -heterocycloalkyl, substituted or unsubstituted C ６～２０ -aryl, and substituted or unsubstituted C ４～２０ -heteroaryl; or R １ and R ３ａ and R ３ｂ or R ｘ and R ３ａ and R ３ｂ or together with the atoms to which they are attached form a ring; Or X is a heteroatom, R ｘ If does not exist, R １ together with form an optionally substituted heterocycle; Y is -SR ａ , -OR ａ , -CR ａ , -NR ａ R ｂ , -PR ａ R ｂ , -P(=O)R ａ R ｂ , -OPR ａ R ｂ , and -NHPR ａ R ｂ Selected from: R ２ and R ｙ are each independently hydrogen, substituted or unsubstituted C １～２０ - alkyl, substituted or unsubstituted C ２～２０ -alkenyl, substituted or unsubstituted C ２～２０ -alkynyl, substituted or unsubstituted C １～２０ -heteroalkyl, substituted or unsubstituted C １～２０ -alkoxy, substituted or unsubstituted C ３～２０ -cycloalkyl, substituted or unsubstituted C ３～２０ -cycloalkenyl, substituted or unsubstituted C ２～２０ -heterocycloalkyl, substituted or unsubstituted C ６～２０ -aryl, and substituted or unsubstituted C ４～２０ -heteroaryl or R ２ and R ４ａ and R ４ｂ or R ｙ and R ４ａ and R ４ｂ or together with the atoms to which they are attached form a ring; or Y is a heteroatom, R ｙ If does not exist, R ２ together with form an optionally substituted heterocycle; R ３ａ , R ３ｂ , R ４ａ , and R ４ｂ are each independently hydrogen, substituted or unsubstituted C １～２０ - alkyl, substituted or unsubstituted C ２～２０ -alkenyl, substituted or unsubstituted C ２～２０ -alkynyl, substituted or unsubstituted C １～２０ -heteroalkyl, substituted or unsubstituted C １～２０ -alkoxy, substituted or unsubstituted C ３～２０ -cycloalkyl, substituted or unsubstituted C ３～２０ -cycloalkenyl, substituted or unsubstituted C ２～２０ -heterocycloalkyl, substituted or unsubstituted C ６～２０ -aryl, and substituted or unsubstituted C ４～２０ -heteroaryl; or R ３ａ and R ４ａ and R ４ｂ or R ３ｂ and R ４ａ and R ４ｂ together with the atoms to which they are attached form a heterocycle; R ５ is hydrogen, substituted or unsubstituted C １～２０ - alkyl, substituted or unsubstituted C ２～２０ -alkenyl, substituted or unsubstituted C ２～２０ -alkynyl, substituted or unsubstituted C １～２０ -heteroalkyl, substituted or unsubstituted C １～２０ -alkoxy, substituted or unsubstituted C ３～２０ -cycloalkyl, substituted or unsubstituted C ３～２０ -cycloalkenyl, substituted or unsubstituted C ２～２０ -heterocycloalkyl, substituted or unsubstituted C ６～２０ -aryl, and substituted or unsubstituted C ４～２０ - selected from heteroaryl; each m and n is independently 1 or 2; and R ａ and R ｂ each independently, if present, is hydrogen, substituted or unsubstituted C １～２０ - alkyl, substituted or unsubstituted C ２～２０ -alkenyl, substituted or unsubstituted C ２～２０ -alkynyl, substituted or unsubstituted C １～２０ -heteroalkyl, substituted or unsubstituted C １～２０ -alkoxy, substituted or unsubstituted C ３～２０ -cycloalkyl, substituted or unsubstituted C ３～２０ -cycloalkenyl, substituted or unsubstituted C ２～２０ -heterocycloalkyl, substituted or unsubstituted C ６～２０ -aryl, and substituted or unsubstituted C ４～２０ -heteroaryl; or X and / or Y are selected from -NR ａ R ｂ , -PR ａ R ｂ , -OPR ａ R ｂ Or -NHPR ａ R ｂ If R ａ and R ｂ form a heterocycle together with the heteroatom to which they are attached.

15. The transition metal catalyst is represented by formula (IV) or formula (V): [M(L) １ )(L ２ ) ｄ ] (UV) [M(L １ )(L ２ ) ｄ ]W (V) (In the formula, M is a transition metal; L １ is a tridentate ligand as defined in claim 14; L ２ are ligands which may be the same or different; d is 1, 2 or 3; and The method of any one of claims 1 to 3 and 5, wherein W is a non-coordinating anionic ligand.

16. 16. The method according to claim 15, wherein M is a transition metal selected from Ru and Os, preferably Ru.

17. Each L ２ are independently -H, -CO, -CN, -P(R') ３ , -As(R') ３ , -CR', -OR', -O(C=O)R', -NR' ２ , a halogen (e.g., -Cl, -Br, -I), and a solvent, where each R' is independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.

18. The transition metal catalyst is 【Chemistry 5】 The method according to any one of claims 1 to 3 and 5,

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